
Professor Lee Smith
Honorary Professor
School of Environmental and Life Sciences
Keeping men healthier
Keeping men healthier for longer will not only improve the quality of life for men as they age, but also save healthcare providers billions of dollars.
Leading the way for reproductive and male health research is Professor Lee Smith, Pro Vice-Chancellor of the College of Engineering, Science and Environment.
Professor Smith, who has an impressive record as an international research innovator in reproductive genetics and endocrinology, is leading a team of University of Newcastle researchers working to understand how testosterone is produced by the body and how it works to promote all aspects of male health.
Testis control of androgen production
“Testosterone is well known for its role in male development, puberty and male fertility, but recent research has identified a much wider range of roles that combine to promote male health.
“Low testosterone is associated with chronic conditions such as diabetes, obesity and cardiovascular disease, and age-related conditions such as frailty, osteoporosis, and muscle-wasting. It has also been linked to an increased risk of early death.
“Testosterone replacement therapy can provide significant benefits to men with low testosterone. Our team is working to leverage this knowledge to develop novel therapies to keep men healthier for longer,” Professor Smith said.
With obesity, ill-health and poor lifestyle habits prevalent in today’s society, Professor Smith hopes that by understanding the complexity of testosterone and cell systems, he’ll be able to develop clinical therapies to help reduce these health issues in men.
“95 per cent of testosterone in men is produced by a single type of cell present only inside the testes – the Leydig cells. Our research focusses on understanding how these cells work, and in particular, how genes and hormones control the production of testosterone by these cells.
“We are working to understand the many cell-types, genes and hormones interacting to both positively and negatively regulate testosterone production, and a myriad of different responses to testosterone levels throughout the body.
“Our novel and unique transgenic approaches are accelerating our understanding towards clinical therapies.
“We can activate or deactivate specific genes inside individual cell-types, track cells throughout development, or remove part or all of an individual cell-type complete. This is advancing the development of viral and nanoparticle gene therapy technologies which deliver new genes to repair damage to the system.
“Our fundamental goal is to understand this system sufficiently to support the development of new therapeutic options for men affected by the multitude of widespread chronic conditions,” he said.
Making new discoveries
With a goal of helping improves lives through his research, Professor Smith is working towards a single treatment approach which will promote long-term health.
“The possibility that a single injection by a GP can improve a man’s health for many years is exciting.
“Our work is taking the most fundamental understanding of knowledge at a genetic and molecular level and turning this into therapies that have the potential to impact millions of lives.
“This knowledge has application in areas such as male development, testis and prostate cancer, male fertility, and chronic clinical conditions such as obesity, diabetes and heart disease.
“Our research goals focus on the future management of healthy ageing in men. Keeping men healthier for longer will not only improve the quality of life for men as they age, but also provide billions of dollars of savings for healthcare providers that can be invested where needed,” he said.
Professor Smith is still driven to make new discoveries – excited for what is next to come.
“Discovery is the most exciting aspect of research. I have on many occasions been fortunate enough – for a brief period of time – to be the only person ever to know that the world works in a certain way. That never gets old!”
Keeping men healthier
Keeping men healthier for longer will not only improve the quality of life for men as they age, but also save healthcare providers billions of dollars.
Career Summary
Biography
Professor Lee Smith began his career with a PhD in Molecular Genetics at the University of Warwick. This was followed by two postdoctoral positions at the MRC Mammalian Genetics Unit in Oxford before moving to Edinburgh in 2006 to lead a program of research within the MRC Human Reproductive Sciences Unit.
In 2012, Lee was appointed to the Chair of Genetic Endocrinology and Principal Investigator at the MRC Centre for Reproductive Health within the University of Edinburgh. In 2016, Lee was promoted to Head of Male Health Research, MRC Centre for Reproductive Health.
Lee moved to the University of Newcastle in early 2017 to take up the positions of Pro Vice-Chancellor, Faculty of Science, and Professor of Endocrine Genetics in the School of Environmental and Life Sciences.
Research Expertise
With a research focus on ‘endocrine control of androgen production’, Lee is focussed on exploiting the stem cell niche within the endocrine system to manipulate androgens as a therapeutic tool for human health benefit. Though responsible for a wide portfoilio of research projects in this area, Lee is perhaps best known for his work examining the role of androgen signalling in male reproductive and other tissues, specifically using cell-specific conditional gene targeting of androgen receptor to reveal a hitherto undescribed complex network of paracrine signalling underpinning control of male tissues.
Teaching Expertise
Lee has lectured from 2007 at the University of Edinburgh in reproductive biology, experimental systems, sex determination, Paracrine signalling module – testis function and male reproductive health. In addition Lee has supervised 20 post-graduate students.
Administrative Expertise
In addition to several administrative roles at the University of Edinburgh, Lee has served on the UK MRC Populations and Systems Medicine Board, and Chaired the inaugural UK MRC national funding panel on Genetically Engineered Mice for Medicine. He has also served as a member of the BBSRC pool of experts. He is a journal referee for in excess of 20 journals and regularly reviews grant applications for international funding panels from across the world.Qualifications
- Doctor of Philosophy, University of Warwick - England
- Bachelor of Science (Honours), University of Leicester - UK
Keywords
- Biotechnology
- Endocrinology
- Fertility regulation
- Genetics
- Infertility
- Reproductive Biology
- Reproductive Sciences
Fields of Research
Code | Description | Percentage |
---|---|---|
320208 | Endocrinology | 50 |
310903 | Animal developmental and reproductive biology | 20 |
440302 | Fertility | 30 |
Professional Experience
UON Appointment
Title | Organisation / Department |
---|---|
Professor | University of Newcastle School of Environmental and Life Sciences Australia |
Academic appointment
Dates | Title | Organisation / Department |
---|---|---|
1/1/2015 - 31/12/2016 | Head of Male Health Research | University of Edinburgh Medical Research Council (MRC) Centre for Reproductive Health United Kingdom |
1/1/2012 - | Personal Chair of Genetic Endocrinology - Principal Investigator | University of Edinburgh Medical Research Council (MRC) Centre for Reproductive Health United Kingdom |
Invitations
Keynote Speaker
Year | Title / Rationale |
---|---|
2015 |
Androgens in lifelong health and wellbeing American Testis Workshop |
Speaker
Year | Title / Rationale |
---|---|
2016 | Androgenic control of male health |
2016 | Viral gene therapy as a single-dose sterilant? |
2016 | Leydig cells: controllers of lifelong male health? |
2016 | How does testosterone influence male health; is it all just sex and violence? |
2016 |
Its time for ‘T’! Testosterone and lifelong male health Public Lecture series |
2015 | Mouse models and male fertility research |
2015 | Androgenic control of male health |
2014 | Paracrine control of testicualr androgen signalling |
2014 | The control of androgen signalling – implications for lifelong male health |
2014 |
The role of Sertoli cells in the prepubertal testis 18th European Testis Workshop |
2014 | Development of a single dose sterilant targeting Androgen Receptor |
2014 | The role of Sertoli cells in the prepubertal testis |
Publications
For publications that are currently unpublished or in-press, details are shown in italics.
Book (1 outputs)
Year | Citation | Altmetrics | Link | ||
---|---|---|---|---|---|
2013 |
Smith LB, Mitchell RT, McEwan IJ, Testosterone: From Basic Research to Clinical Applications, Springer New York (2013)
|
Chapter (6 outputs)
Year | Citation | Altmetrics | Link | ||||||||
---|---|---|---|---|---|---|---|---|---|---|---|
2018 |
McEwan IJ, Smith LB, 'Androgen receptor', Encyclopedia of Reproduction 222-226 (2018) The majority of physiological actions of testosterone and dihydrotestosterone are mediated by the androgen receptor, a member of the nuclear receptor superfamily, encoded as a sin... [more] The majority of physiological actions of testosterone and dihydrotestosterone are mediated by the androgen receptor, a member of the nuclear receptor superfamily, encoded as a single gene on the X-chromosome. Androgen receptor has four functional domains, N-terminal, DNA binding, hinge and ligand binding. In response to hormone binding the androgen receptor protein positively or negatively regulates gene expression (classical pathway) or signaling cascade activity (nonclassical pathway) in target tissues. Androgen receptor is long known to be essential for correct masculinization, and male fertility, however recent studies have identified novel influences androgen receptor plays in both lifelong health, and disease.
|
||||||||||
2018 |
Rebourcet D, Darbey A, Curley M, O Shaughnessy P, Smith LB, 'Testicular cell selective ablation using diphtheria toxin receptor transgenic mice', Sertoli Cells: Methods and Protocols, Humana Press, New York, NY 203-228 (2018) [B1]
|
||||||||||
2017 | O'Hara L, Smith LB, 'Mouse Genetics: how does it inform male fertility research?', The Sperm Cell Production, Maturation, Fertilization, Regeneration, Cambridge University Press, Cambridge, UK (2017) | ||||||||||
2015 |
Smith LB, Walker WH, 'Hormone Signaling in the Testis', Knobil and Neill's Physiology of Reproduction: Two-Volume Set 637-690 (2015) A complex milieu of hormones initiates diverse signaling pathways within and between cells of the testis to support the processes of steroidogenesis, spermatogenesis, and ultimate... [more] A complex milieu of hormones initiates diverse signaling pathways within and between cells of the testis to support the processes of steroidogenesis, spermatogenesis, and ultimately male fertility. In this chapter, we discuss the roles, mechanisms, and impacts of hormone signaling within the testis. We describe the mechanisms by which luteinizing hormone promotes the production of testosterone, a hormone essential for spermatogenesis. We use information obtained from cell-specific knockout studies of the androgen receptor as well as cellular and gene expression studies to describe the multifaceted actions of testosterone within the testis. We examine the multiple signaling pathways regulated by follicle-stimulating hormone in Sertoli cells and discuss how these pathways interface with testosterone signaling. In addition, we review how thyroid hormone regulates the proliferation of Sertoli cells and thus determines the capacity for sperm production. Furthermore, the paracrine functions of testis-derived hormones, including estrogen as well as activin and inhibin, are discussed. Finally, the contributions of other hormones that act to fine-tune testicular functions in response to environmental inputs are discussed. Together, these combined data paint a vivid picture of a complex, hormone-regulated signaling environment in the testis that acts to ensure that correct testicular function is maintained throughout life.
|
||||||||||
Show 3 more chapters |
Journal article (103 outputs)
Year | Citation | Altmetrics | Link | ||||||||
---|---|---|---|---|---|---|---|---|---|---|---|
2022 |
Curley M, Darbey A, O'Donnell L, Kilcoyne KR, Wilson K, Mungall W, et al., 'Leukemia inhibitory factor-receptor signalling negatively regulates gonadotrophin-stimulated testosterone production in mouse Leydig Cells: LIFR Signalling in Leydig Cells', Molecular and Cellular Endocrinology, 544 (2022) Testicular Leydig cells (LCs) are the principal source of circulating testosterone in males. LC steroidogenesis maintains sexual function, fertility and general health, and is inf... [more] Testicular Leydig cells (LCs) are the principal source of circulating testosterone in males. LC steroidogenesis maintains sexual function, fertility and general health, and is influenced by various paracrine factors. The leukemia inhibitory factor receptor (LIFR) is expressed in the testis and activated by different ligands, including leukemia inhibitory factor (LIF), produced by peritubular myoid cells. LIF can modulate LC testosterone production in vitro under certain circumstances, but the role of consolidated signalling through LIFR in adult LC function in vivo has not been established. We used a conditional Lifr allele in combination with adenoviral vectors expressing Cre-recombinase to generate an acute model of LC Lifr-KO in the adult mouse testis, and showed that LC Lifr is not required for short term LC survival or basal steroidogenesis. However, LIFR-signalling negatively regulates steroidogenic enzyme expression and maximal gonadotrophin-stimulated testosterone biosynthesis, expanding our understanding of the intricate regulation of LC steroidogenic function.
|
||||||||||
2022 |
O'Donnell L, Smith LB, Rebourcet D, 'Sertoli cells as key drivers of testis function', Seminars in Cell and Developmental Biology, 121 2-9 (2022) Sertoli cells are the orchestrators of spermatogenesis; they support fetal germ cell commitment to the male pathway and are essential for germ cell development, from maintenance o... [more] Sertoli cells are the orchestrators of spermatogenesis; they support fetal germ cell commitment to the male pathway and are essential for germ cell development, from maintenance of the spermatogonial stem cell niche and spermatogonial populations, through meiosis and spermiogeneis and to the final release of mature spermatids during spermiation. However, Sertoli cells are also emerging as key regulators of other testis somatic cells, including supporting peritubular myoid cell development in the pre-pubertal testis and supporting the function of the testicular vasculature and in contributing to testicular immune privilege. Sertoli cells also have a major role in regulating androgen production within the testis, by specifying interstitial cells to a steroidogenic fate, contributing to androgen production in the fetal testis, and supporting fetal and adult Leydig cell development and function. Here, we provide an overview of the specific roles for Sertoli cells in the testis and highlight how these cells are key drivers of testicular sperm output, and of adult testis size and optimal function of other testicular somatic cells, including the steroidogenic Leydig cells.
|
||||||||||
2021 |
Gannon AL, O Hara L, Mason IJ, Jørgensen A, Frederiksen H, Curley M, et al., 'Androgen Receptor Is Dispensable for X-Zone Regression in the Female Adrenal but Regulates Post-Partum Corticosterone Levels and Protects Cortex Integrity', Frontiers in Endocrinology, 11 (2021) [C1] Adrenal androgens are fundamental mediators of ovarian folliculogenesis, embryonic implantation, and breast development. Although adrenal androgen function in target tissues are w... [more] Adrenal androgens are fundamental mediators of ovarian folliculogenesis, embryonic implantation, and breast development. Although adrenal androgen function in target tissues are well characterized, there is little research covering the role of androgen-signaling within the adrenal itself. Adrenal glands express AR which is essential for the regression of the X-zone in male mice. Female mice also undergo X-zone regression during their first pregnancy, however whether this is also controlled by AR signaling is unknown. To understand the role of the androgen receptor (AR) in the female adrenal, we utilized a Cyp11a1-Cre to specifically ablate AR from the mouse adrenal cortex. Results show that AR-signaling is dispensable for adrenal gland development in females, and for X-zone regression during pregnancy, but is required to suppress elevation of corticosterone levels post-partum. Additionally, following disruption to adrenal AR, aberrant spindle cell development is observed in young adult females. These results demonstrate sexually dimorphic regulation of the adrenal X-zone by AR and point to dysfunctional adrenal androgen signaling as a possible mechanism in the early development of adrenal spindle cell hyperplasia.
|
||||||||||
2021 |
O'Donnell L, Rebourcet D, Dagley LF, Sgaier R, Infusini G, O'Shaughnessy PJ, et al., 'Sperm proteins and cancer-testis antigens are released by the seminiferous tubules in mice and men', FASEB Journal, 35 (2021) [C1] Sperm develop from puberty in the seminiferous tubules, inside the blood-testis barrier to prevent their recognition as ¿non-self¿ by the immune system, and it is widely assumed t... [more] Sperm develop from puberty in the seminiferous tubules, inside the blood-testis barrier to prevent their recognition as ¿non-self¿ by the immune system, and it is widely assumed that human sperm-specific proteins cannot access the circulatory or immune systems. Sperm-specific proteins aberrantly expressed in cancer, known as cancer-testis antigens (CTAs), are often pursued as cancer biomarkers and therapeutic targets based on the assumption they are neoantigens absent from the circulation in healthy men. Here, we identify a wide range of germ cell-derived and sperm-specific proteins, including multiple CTAs, that are selectively deposited by the Sertoli cells of the adult mouse and human seminiferous tubules into testicular interstitial fluid (TIF) that is ¿outside¿ the blood-testis barrier. From TIF, the proteins can access the circulatory- and immune systems. Disruption of spermatogenesis decreases the abundance of these proteins in mouse TIF, and a sperm-specific CTA is significantly decreased in TIF from infertile men, suggesting that exposure of certain CTAs to the immune system could depend on fertility status. The results provide a rationale for the development of blood-based tests useful in the management of male infertility and indicate CTA candidates for cancer immunotherapy and biomarker development that could show sex-specific and male-fertility-related responses.
|
||||||||||
2021 |
Wang TE, Minabe S, Matsuda F, Li SH, Tsukamura H, Maeda KI, et al., 'Testosterone regulation on quiescin sulfhydryl oxidase 2 synthesis in the epididymis', Reproduction, 161 593-602 (2021) [C1] The epididymis is an androgen-responsive organ, whose structure and functions are modulated by the coordination between androgen and epididymal cues. Highly regulated molecular in... [more] The epididymis is an androgen-responsive organ, whose structure and functions are modulated by the coordination between androgen and epididymal cues. Highly regulated molecular interaction within the epididymis is required to support viable sperm development necessary for subsequent fertilization. In the present study, we extended our earlier findings on a promising epididymal protein, quiescin sulfhydryl oxidase 2 (QSOX2), and demonstrated a positive correlation between testosterone and QSOX2 protein synthesis through the use of loss- and restore-of-function animal models. Moreover, based on transcriptomic analyses and 2D culture system, we determined that an additional polarized effect of glutamate is indispensable for the regulatory action of testosterone on QSOX2 synthesis. In conclusion, we propose noncanonical testosterone signaling supports epididymal QSOX2 protein synthesis, providing a novel perspective on the regulation of sperm maturation within the epididymis.
|
||||||||||
2021 |
O'Hara L, Christian HC, Le Tissier P, Smith LB, 'Hyperprolactinemia in a male pituitary androgen receptor knockout mouse is associated with female-like lactotroph development', ANDROLOGY, 9 1652-1661 (2021)
|
||||||||||
2021 |
Sararols P, Stevant I, Neirijnck Y, Rebourcet D, Darbey A, Curley MK, et al., 'Specific Transcriptomic Signatures and Dual Regulation of Steroidogenesis Between Fetal and Adult Mouse Leydig Cells', FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY, 9 (2021)
|
||||||||||
2020 |
O'Hara L, Christian HC, Jeffery N, Le Tissier P, Smith LB, 'Characterisation of a mural cell network in the murine pituitary gland', Journal of Neuroendocrinology, 32 (2020) [C1]
|
||||||||||
2020 |
Rebourcet D, Mackay R, Darbey A, Curley MK, Jørgensen A, Frederiksen H, et al., 'Ablation of the canonical testosterone production pathway via knockout of the steroidogenic enzyme HSD17B3, reveals a novel mechanism of testicular testosterone production', FASEB Journal, 34 10373-10386 (2020) [C1]
|
||||||||||
2020 |
Darbey A, Rebourcet D, Curley M, Kilcoyne K, Jeffery N, Reed N, et al., 'A comparison of in vivo viral targeting systems identifies adeno-associated virus serotype 9 (AAV9) as an effective vector for genetic manipulation of Leydig cells in adult mice', ANDROLOGY, 9 460-473 (2020) [C1]
|
||||||||||
2020 |
Smart E, Macdonald J, Smith LB, Mitchell RT, 'Reconstitution of rat fetal testis during the masculinisation programming window induces focal dysgenesis consistent with testicular dysgenesis syndrome', Scientific Reports, 10 (2020) [C1] Focal dysgenesis is a consistent feature of testicular dysgenesis syndrome (TDS) in humans. Rodent studies show that perturbation of androgens (e.g. following phthalate exposure) ... [more] Focal dysgenesis is a consistent feature of testicular dysgenesis syndrome (TDS) in humans. Rodent studies show that perturbation of androgens (e.g. following phthalate exposure) during a fetal masculinisation programming window (MPW) predisposes to a TDS phenotype. This study aimed to determine whether dissociation and reconstitution of rat fetal testis tissue during the MPW can be used to model and manipulate seminiferous cord development, including induction of focal dysgenesis, as described in TDS. Dissociated fetal rat testes were xenotransplanted subcutaneously into recipient mice for 4¿weeks. Transplanted mice were treated with vehicle or di-n-butyl-phthalate (DBP, a plasticising chemical known to induce testicular dysgenesis in vivo in rats). Testosterone production by the transplants was measured in recipient mice and immunofluorescence was performed on the retrieved transplants to identify features consistent with focal testicular dysgenesis. Re-aggregation of rat fetal testis tissue xenotransplants during the MPW results in reconstitution of seminiferous cords. Features of focal testicular dysgenesis were present in re-aggregated testis, including ectopic Sertoli cells and intratubular Leydig cells (ITLCs). DBP exposure of recipient mice reduced androgen-dependent seminal vesicle weight (8.3 vs 26.7¿mg; p < 0.05), but did not enhance features of focal dysgenesis including number of ITLCs (0.07 vs 0.10 cells/mm2; p > 0.05). We conclude that¿seminiferous cord reformation during the MPW results in development of focal dysgenesis. The system may be used to separate specific effects (e.g. androgen suppression) of individual chemical exposures from other mechanisms that may be conserved in TDS.
|
||||||||||
2020 |
Hutka M, Kadam P, Van Saen D, Homer NZM, Onofre J, Wallace WHB, et al., 'Fertility Preservation in Childhood Cancer: Endocrine Activity in Prepubertal Human Testis Xenografts Exposed to a Pubertal Hormone Environment.', Cancers, 12 (2020) [C1]
|
||||||||||
2020 |
Hutka M, Smith LB, Goossens E, Wallace WHB, Stukenborg J-B, Mitchell RT, 'Exogenous Gonadotrophin Stimulation Induces Partial Maturation of Human Sertoli Cells in a Testicular Xenotransplantation Model for Fertility Preservation', Journal of Clinical Medicine, 9 (2020) [C1]
|
||||||||||
2019 |
Curley M, Milne L, Smith S, Jørgensen A, Frederiksen H, Hadoke P, et al., 'A young testicular microenvironment protects Leydig cells against age-related dysfunction in a mouse model of premature aging', FASEB Journal, 33 978-995 (2019) [C1]
|
||||||||||
2019 |
Gannon A-L, O'Hara L, Mason JI, Jorgensen A, Frederiksen H, Milne L, et al., 'Androgen receptor signalling in the male adrenal facilitates X-zone regression, cell turnover and protects against adrenal degeneration during ageing', SCIENTIFIC REPORTS, 9 (2019) [C1]
|
||||||||||
2019 |
Rebourcet D, Monteiro A, Cruickshanks L, Jeffery N, Smith S, Milne L, et al., 'Relationship of transcriptional markers to Leydig cell number in the mouse testis', PloS one, 14 (2019) [C1]
|
||||||||||
2019 |
O'Shaughnessy PJ, Mitchell RT, Monteiro A, O'Hara L, Cruickshanks L, Claahsen-van der Grinten H, et al., 'Androgen receptor expression is required to ensure development of adult Leydig cells and to prevent development of steroidogenic cells with adrenal characteristics in the mouse testis', BMC DEVELOPMENTAL BIOLOGY, 19 (2019) [C1]
|
||||||||||
2019 |
Curley M, Gonzalez ZN, Milne L, Hadoke P, Handel I, Peault B, Smith LB, 'Human Adipose-derived Pericytes Display Steroidogenic Lineage Potential in Vitro and Influence Leydig Cell Regeneration in Vivo in Rats', SCIENTIFIC REPORTS, 9 (2019) [C1]
|
||||||||||
2019 |
Gannon A-L, O'Hara L, Mason JI, Rebourcet D, Smith S, Traveres A, et al., 'Ablation of glucocorticoid receptor in the hindbrain of the mouse provides a novel model to investigate stress disorders', SCIENTIFIC REPORTS, 9 (2019) [C1]
|
||||||||||
2019 |
Rebourcet D, O'Shaughnessy PJ, Smith LB, 'The expanded roles of Sertoli cells: lessons from Sertoli cell ablation models', Current Opinion in Endocrine and Metabolic Research, 6 42-48 (2019) [C1]
|
||||||||||
2018 |
Banks G, Lassi G, Hoerder-Suabedissen A, Tinarelli F, Simon MM, Wilcox A, et al., 'A missense mutation in Katnal1 underlies behavioural, neurological and ciliary anomalies', MOLECULAR PSYCHIATRY, 23 713-722 (2018) [C1]
|
||||||||||
2018 |
Kasak L, Punab M, Nagirnaja L, Grigorova M, Minajeva A, Lopes AM, et al., 'Bi-allelic Recessive Loss-of-Function Variants in FANCM Cause Non-obstructive Azoospermia', American Journal of Human Genetics, 103 200-212 (2018) [C1]
|
||||||||||
2018 |
Takov K, Wu J, Denvir MA, Smith LB, Hadoke PWF, 'The role of androgen receptors in atherosclerosis', Molecular and Cellular Endocrinology, 465 82-91 (2018) [C1]
|
||||||||||
2018 |
Neirijnck Y, Calvel P, Kilcoyne KR, Kühne F, Stévant I, Griffeth RJ, et al., 'Insulin and IGF1 receptors are essential for the development and steroidogenic function of adult Leydig cells.', FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 32 3321-3335 (2018) [C1]
|
||||||||||
2018 |
O'Hara L, O'Shaughnessy PJ, Freeman TC, Smith LB, 'Modelling steroidogenesis: A framework model to support hypothesis generation and testing across endocrine studies', BMC Research Notes, 11 (2018) [C1]
|
||||||||||
2018 |
Pridans C, Raper A, Davis GM, Alves J, Sauter KA, Lefevre L, et al., 'Pleiotropic Impacts of Macrophage and Microglial Deficiency on Development in Rats with Targeted Mutation of the Csf1r Locus.', Journal of Immunology, 201 2683-2699 (2018) [C1]
|
||||||||||
2018 |
Darbey A, Smith LB, 'Deliverable transgenics & gene therapy possibilities for the testes', Molecular and Cellular Endocrinology, 468 81-94 (2018) [C1]
|
||||||||||
2018 |
Livigni A, O'Hara L, Polak ME, Angus T, Wright DW, Smith LB, Freeman TC, 'A graphical and computational modeling platform for biological pathways.', Nature protocols, 13 705-722 (2018) [C1]
|
||||||||||
2018 |
Macdonald J, Kilcoyne KR, Sharpe RM, Kavanagh Á, Anderson RA, Brown P, et al., 'DMRT1 repression using a novel approach to genetic manipulation induces testicular dysgenesis in human fetal gonads', HUMAN REPRODUCTION, 33 2107-2121 (2018) [C1]
|
||||||||||
2018 |
Stevant I, Neirijnck Y, Borel C, Escoffier J, Smith LB, Antonarakis SE, et al., 'Deciphering Cell Lineage Specification during Male Sex Determination with Single-Cell RNA Sequencing', CELL REPORTS, 22 1589-1599 (2018) [C1]
|
||||||||||
2018 |
Curley M, Milne L, Smith S, Atanassova N, Rebourcet D, Darbey A, et al., 'Leukemia Inhibitory Factor-Receptor is Dispensable for Prenatal Testis Development but is Required in Sertoli cells for Normal Spermatogenesis in Mice', SCIENTIFIC REPORTS, 8 (2018) [C1]
|
||||||||||
2017 |
Hutka M, Smith LB, Mitchell RT, 'Xenotransplantation as a model for human testicular development', Differentiation, 97 44-53 (2017) [C1] The developing male reproductive system may be sensitive to disruption by a wide range of exogenous ¿endocrine disruptors¿. In-utero exposure to environmental chemicals and pharma... [more] The developing male reproductive system may be sensitive to disruption by a wide range of exogenous ¿endocrine disruptors¿. In-utero exposure to environmental chemicals and pharmaceuticals have been hypothesized to have an impact in the increasing incidence of male reproductive disorders. The vulnerability to adverse effects as a consequence of such exposures is elevated during a specific ¿window of susceptibility¿ in fetal life referred to as the masculinisation programing window (MPW). Exposures that occur during prepuberty, such as chemotherapy treatment for cancer during childhood, may also affect future fertility. Much of our current knowledge about fetal and early postnatal human testicular development derives from studies conducted in animal models predictive for humans. Therefore, over recent years, testicular transplantation has been employed as a ¿direct¿ approach to understand the development of human fetal and prepubertal testis in health and disease. In this review we describe the potential use of human testis xenotransplantation to study testicular development and its application for (i) assessing the effects of environmental exposures in humans, and (ii) establishing fertility preservation options for prepubertal boys with cancer.
|
||||||||||
2017 |
Soffientini U, Rebourcet D, Abel MH, Lee S, Hamilton G, Fowler PA, et al., 'Identification of Sertoli cell-specific transcripts in the mouse testis and the role of FSH and androgen in the control of Sertoli cell activity', BMC GENOMICS, 18 (2017) [C1]
|
||||||||||
2017 |
Rebourcet D, Darbey A, Monteiro A, Soffientini U, Tsai YT, Handel I, et al., 'Sertoli Cell Number Defines and Predicts Germ and Leydig Cell Population Sizes in the Adult Mouse Testis', ENDOCRINOLOGY, 158 2955-2969 (2017) [C1]
|
||||||||||
2017 |
Patel SH, O'Hara L, Atanassova N, Smith SE, Curley MK, Rebourcet D, et al., 'Low-dose tamoxifen treatment in juvenile males has long-term adverse effects on the reproductive system: implications for inducible transgenics.', Scientific Reports, 7 (2017) [C1]
|
||||||||||
2015 |
Mitchell RT, Mungall W, McKinnell C, Sharpe RM, Cruickshanks L, Milne L, Smith LB, 'Anogenital Distance Plasticity in Adulthood: Implications for Its Use as a Biomarker of Fetal Androgen Action', ENDOCRINOLOGY, 156 24-31 (2015) [C1]
|
||||||||||
2015 |
O'Hara L, McInnes K, Simitsidellis I, Morgan S, Atanassova N, Slowikowska-Hilczer J, et al., 'Autocrine androgen action is essential for Leydig cell maturation and function, and protects against late-onset Leydig cell apoptosis in both mice and men', FASEB JOURNAL, 29 894-910 (2015) [C1]
|
||||||||||
2015 |
Willems A, Roesl C, Mitchell RT, Milne L, Jeffery N, Smith S, et al., 'Sertoli Cell Androgen Receptor Signalling in Adulthood Is Essential for Post-Meiotic Germ Cell Development', MOLECULAR REPRODUCTION AND DEVELOPMENT, 82 626-627 (2015) [C1]
|
||||||||||
2015 |
Fijak M, Damm L-J, Wenzel J-P, Aslani F, Walecki M, Wahle E, et al., 'Influence of Testosterone on Inflammatory Response in Testicular Cells and Expression of Transcription Factor Foxp3 in T Cells', AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, 74 12-25 (2015) [C1]
|
||||||||||
2015 |
O'Hara L, Smith LB, 'Androgen receptor roles in spermatogenesis and infertility', BEST PRACTICE & RESEARCH CLINICAL ENDOCRINOLOGY & METABOLISM, 29 595-605 (2015) [C1]
|
||||||||||
2015 |
Guillermet-Guibert J, Smith LB, Halet G, Whitehead MA, Pearce W, Rebourcet D, et al., 'Novel Role for p110 beta PI 3-Kinase in Male Fertility through Regulation of Androgen Receptor Activity in Sertoli Cells', PLOS GENETICS, 11 (2015) [C1]
|
||||||||||
2015 |
O'Hara L, Curley M, Ferreira MT, Cruickshanks L, Milne L, Smith LB, 'Pituitary Androgen Receptor Signalling Regulates Prolactin but Not Gonadotrophins in the Male Mouse', PLOS ONE, 10 (2015) [C1]
|
||||||||||
2015 |
van den Driesche S, Macdonald J, Anderson RA, Johnston ZC, Chetty T, Smith LB, et al., 'Prolonged exposure to acetaminophen reduces testosterone production by the human fetal testis in a xenograft model', SCIENCE TRANSLATIONAL MEDICINE, 7 (2015) [C1]
|
||||||||||
2015 |
Smith LB, O'Shaughnessy PJ, Rebourcet D, 'Cell-specific ablation in the testis: what have we learned?', ANDROLOGY, 3 1035-1049 (2015) [C1]
|
||||||||||
2014 |
Mitchell RT, E Camacho-Moll M, Macdonald J, Anderson RA, Kelnar CJH, E Camacho-Moll M, et al., 'Intratubular germ cell neoplasia of the human testis: heterogeneous protein expression and relation to invasive potential', Modern Pathology, (2014) [C1] Testicular germ cell cancer develops from premalignant intratubular germ cell neoplasia, unclassified cells that are believed to arise from failure of normal maturation of fetal g... [more] Testicular germ cell cancer develops from premalignant intratubular germ cell neoplasia, unclassified cells that are believed to arise from failure of normal maturation of fetal germ cells from gonocytes (OCT4 + /MAGEA4 - ) into pre-spermatogonia (OCT4 - /MAGEA4 + ). Intratubular germ cell neoplasia cell subpopulations based on stage of germ cell differentiation have been described, however the importance of these subpopulations in terms of invasive potential has not been reported. We hypothesized that cells expressing an immature (OCT4 + /MAGEA4 - ) germ cell profile would exhibit an increased proliferation rate compared with those with a mature profile (OCT4 + /MAGEA4 + ). Therefore, we performed triple immunofluorescence and stereology to quantify the different intratubular germ cell neoplasia cell subpopulations, based on expression of germ cell (OCT4, PLAP, AP2¿, MAGEA4, VASA) and proliferation (Ki67) markers, in testis sections from patients with preinvasive disease, seminoma, and non-seminoma. We compared these subpopulations with normal human fetal testis and with seminoma cells. Heterogeneity of protein expression was demonstrated in intratubular germ cell neoplasia cells with respect to gonocyte and spermatogonial markers. It included an embryonic/fetal germ cell subpopulation lacking expression of the definitive intratubular germ cell neoplasia marker OCT4, that did not correspond to a physiological (fetal) germ cell subpopulation. OCT4 + /MAGEA4 - cells showed a significantly increased rate of proliferation compared with the OCT4 + /MAGEA4 + population (12.8 versus 3.4%, P < 0.0001) irrespective of histological tumor type, reflected in the predominance of OCT4 + /MAGEA4 - cells in the invasive tumor component. Surprisingly, OCT4 + /MAGEA4 - cells in patients with preinvasive disease showed significantly higher proliferation compared to those with seminoma or non-seminoma (18.1 versus 10.2 versus 7.2%, P < 0.05, respectively). In conclusion, this study has demonstrated that OCT4 + /MAGEA4 - cells are the most frequent and most proliferative cell population in tubules containing intratubular germ cell neoplasia, which appears to be an important factor in determining invasive potential of intratubular germ cell neoplasia to seminomas.Modern Pathology advance online publication, 24 January 2014; doi:10.1038/modpathol.2013.246.
|
||||||||||
2014 |
Wu J, Hadoke PWF, Mair I, Lim WG, Miller E, Denvir MA, Smith LB, 'Modulation of neointimal lesion formation by endogenous androgens is independent of vascular androgen receptor', CARDIOVASCULAR RESEARCH, 103 281-290 (2014) [C1]
|
||||||||||
2014 |
Kilcoyne KR, Smith LB, Atanassova N, Macpherson S, McKinnell C, van den Driesche S, et al., 'Fetal programming of adult Leydig cell function by androgenic effects on stem/progenitor cells', PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 111 E1924-E1932 (2014) [C1]
|
||||||||||
2014 |
Sauter KA, Pridans C, Sehgal A, Tsai YT, Bradford BM, Raza S, et al., 'Pleiotropic effects of extended blockade of CSF1R signaling in adult mice', JOURNAL OF LEUKOCYTE BIOLOGY, 96 265-274 (2014) [C1]
|
||||||||||
2014 |
Rebourcet D, O'Shaughnessy PJ, Pitetti J-L, Monteiro A, O'Hara L, Milne L, et al., 'Sertoli cells control peritubular myoid cell fate and support adult Leydig cell development in the prepubertal testis', DEVELOPMENT, 141 2139-2149 (2014) [C1]
|
||||||||||
2014 |
Smith LB, Walker WH, 'The regulation of spermatogenesis by androgens', SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY, 30 2-13 (2014) [C1]
|
||||||||||
2014 |
Gow DJ, Sauter KA, Pridans C, Moffat L, Sehgal A, Stutchfield BM, et al., 'Characterisation of a Novel Fc Conjugate of Macrophage Colony-stimulating Factor', MOLECULAR THERAPY, 22 1580-1592 (2014) [C1]
|
||||||||||
2014 |
O'Hara L, York JP, Zhang P, Smith LB, 'Targeting of GFP-Cre to the Mouse Cyp11a1 Locus Both Drives Cre Recombinase Expression in Steroidogenic Cells and Permits Generation of Cyp11a1 Knock Out Mice', PLOS ONE, 9 (2014) [C1]
|
||||||||||
2014 |
Rebourcet D, O'Shaughnessy PJ, Monteiro A, Milne L, Cruickshanks L, Jeffrey N, et al., 'Sertoli Cells Maintain Leydig Cell Number and Peritubular Myoid Cell Activity in the Adult Mouse Testis', PLOS ONE, 9 (2014) [C1]
|
||||||||||
2014 |
Zimmermann C, Romero Y, Warnefors M, Bilican A, Borel C, Smith LB, et al., 'Germ Cell-Specific Targeting of DICER or DGCR8 Reveals a Novel Role for Endo-siRNAs in the Progression of Mammalian Spermatogenesis and Male Fertility', PLOS ONE, 9 (2014) [C1]
|
||||||||||
2013 |
Hall EA, Keighren M, Ford MJ, Davey T, Jarman AP, Smith LB, et al., 'Acute Versus Chronic Loss of Mammalian Azi1/Cep131 Results in Distinct Ciliary Phenotypes', PLOS GENETICS, 9 (2013) [C1]
|
||||||||||
2013 |
Mitchell RT, Sharpe RM, Anderson RA, McKinnell C, Macpherson S, Smith LB, et al., 'Diethylstilboestrol Exposure Does Not Reduce Testosterone Production in Human Fetal Testis Xenografts', PLOS ONE, 8 (2013) [C1]
|
||||||||||
2012 |
McInnes KJ, Smith LB, Hunger NI, Saunders PTK, Andrew R, Walker BR, 'Deletion of the Androgen Receptor in Adipose Tissue in Male Mice Elevates Retinol Binding Protein 4 and Reveals Independent Effects on Visceral Fat Mass and on Glucose Homeostasis', DIABETES, 61 1072-1081 (2012) [C1]
|
||||||||||
2012 |
Welsh M, Moffat L, Belling K, de Franca LR, Segatelli TM, Saunders PTK, et al., 'Androgen receptor signalling in peritubular myoid cells is essential for normal differentiation and function of adult Leydig cells', INTERNATIONAL JOURNAL OF ANDROLOGY, 35 25-40 (2012) [C1]
|
||||||||||
2012 |
Dean A, Smith LB, Macpherson S, Sharpe RM, 'The effect of dihydrotestosterone exposure during or prior to the masculinization programming window on reproductive development in male and female rats', INTERNATIONAL JOURNAL OF ANDROLOGY, 35 330-339 (2012) [C1]
|
||||||||||
2012 |
Smith LB, Milne L, Nelson N, Eddie S, Brown P, Atanassova N, et al., 'KATNAL1 Regulation of Sertoli Cell Microtubule Dynamics Is Essential for Spermiogenesis and Male Fertility', PLOS GENETICS, 8 (2012) [C1]
|
||||||||||
2012 |
O'Donnell L, Rhodes D, Smith SJ, Merriner DJ, Clark BJ, Borg C, et al., 'An Essential Role for Katanin p80 and Microtubule Severing in Male Gamete Production', PLOS GENETICS, 8 (2012) [C1]
|
||||||||||
2012 |
van den Driesche S, Walker M, McKinnell C, Scott HM, Eddie SL, Mitchell RT, et al., 'Proposed Role for COUP-TFII in Regulating Fetal Leydig Cell Steroidogenesis, Perturbation of Which Leads to Masculinization Disorders in Rodents', PLOS ONE, 7 (2012) [C1]
|
||||||||||
2012 |
O'Hara L, Smith LB, 'Androgen receptor signalling in Vascular Endothelial cells is dispensable for spermatogenesis and male fertility', BMC Research Notes, 5 (2012) [C1] Background: Androgen signalling is essential both for male development and function of the male reproductive system in adulthood. Within the adult testis, Germ cells (GC) do not e... [more] Background: Androgen signalling is essential both for male development and function of the male reproductive system in adulthood. Within the adult testis, Germ cells (GC) do not express androgen receptor (AR) suggesting androgen-mediated promotion of spermatogenesis must act via AR-expressing somatic cell-types. Several recent studies have exploited the Cre/lox system of conditional gene-targeting to ablate AR function from key somatic cell-types in order to establish the cell-specific role of AR in promotion of male fertility. In this study, we have used a similar approach to specifically ablate AR-signalling from Vascular Endothelial (VE) cells, with a view to defining the significance of androgen signalling within this cell-type on spermatogenesis. Findings. AR expression in VE cells of the testicular vasculature was confirmed using an antibody against AR. A Cre-inducible fluorescent reporter line was used to empirically establish the utility of a mouse line expressing Cre Recombinase driven by the Tie2-Promoter, for targeting VE cells. Immunofluorescent detection revealed expression of YFP (and therefore Cre Recombinase function) limited to VE cells and an interstitial population of cells, believed to be macrophages, that did not express AR. Mating of Tie2-Cre males to females carrying a floxed AR gene produced Vascular Endothelial Androgen Receptor Knockout (VEARKO) mice and littermate controls. Ablation of AR from all VE cells was confirmed; however, no significant differences in bodyweight or reproductive tissue weights could be detected in VEARKO animals and spermatogenesis and fertility was unaffected. Conclusions: We demonstrate the successful generation and empirical validation of a cell-specific knockout of AR from VE cells, and conclude that AR expression in VE cells is not essential for spermatogenesis or male fertility. © 2012 O'Hara et al.
|
||||||||||
2011 |
Smith LB, Hadoke PWF, Dyer E, Denvir MA, Brownstein D, Miller E, et al., 'Haploinsufficiency of the murine Col3a1 locus causes aortic dissection: a novel model of the vascular type of Ehlers-Danlos syndrome', CARDIOVASCULAR RESEARCH, 90 182-190 (2011) [C1]
|
||||||||||
2011 |
O'Hara L, Welsh M, Saunders PTK, Smith LB, 'Androgen Receptor Expression in the Caput Epididymal Epithelium Is Essential for Development of the Initial Segment and Epididymal Spermatozoa Transit', ENDOCRINOLOGY, 152 718-729 (2011) [C1]
|
||||||||||
2011 |
Welsh M, Moffat L, McNeilly A, Brownstein D, Saunders PTK, Sharpe RM, Smith LB, 'Smooth Muscle Cell-Specific Knockout of Androgen Receptor: A New Model for Prostatic Disease', ENDOCRINOLOGY, 152 3541-3551 (2011) [C1]
|
||||||||||
2011 |
Smith LB, Saunders PTK, 'The Skeleton: The New Controller of Male Fertility?', CELL, 144 642-+ (2011)
|
||||||||||
2011 |
Orr B, Vanpoucke G, Grace OC, Smith L, Anderson RA, Riddick ACP, et al., 'Expression of pleiotrophin in the prostate is androgen regulated and it functions as an autocrine regulator of mesenchyme and cancer associated fibroblasts and as a paracrine regulator of epithelia', Prostate, 71 305-317 (2011) [C1] BACKGROUND Androgens and paracrine signaling from mesenchyme/stroma regulate development and disease of the prostate, and gene profiling studies of inductive prostate mesenchyme h... [more] BACKGROUND Androgens and paracrine signaling from mesenchyme/stroma regulate development and disease of the prostate, and gene profiling studies of inductive prostate mesenchyme have identified candidate molecules such as pleiotrophin (Ptn). METHODS Ptn transcripts and protein were localized by in situ and immunohistochemistry and Ptn mRNA was quantitated by Northern blot and qRT-PCR. Ptn function was examined by addition of hPTN protein to rat ventral prostate organ cultures, primary human fetal prostate fibroblasts, prostate cancer associated fibroblasts, and BPH1 epithelia. RESULTS During development, Ptn transcripts and protein were expressed in ventral mesenchymal pad (VMP) and prostatic mesenchyme. Ptn was localized to mesenchyme surrounding ductal epithelial tips undergoing branching morphogenesis, and was located on the surface of epithelia. hPTN protein stimulated branching morphogenesis and stromal and epithelial proliferation, when added to rat VP cultures, and also stimulated growth of fetal human prostate fibroblasts, prostate cancer associated fibroblasts, and BPH1 epithelia. PTN mRNA was enriched in patient-matched normal prostate fibroblasts versus prostate cancer associated fibroblasts. PTN also showed male enriched expression in fetal human male urethra versus female, and between wt male and ARKO male mice. Transcripts for PTN were upregulated by testosterone in fetal human prostate fibroblasts and organ cultures of female rat VMP. Ptn protein was increased by testosterone in organ cultures of female rat VMP and in rat male urethra compared to female. CONCLUSIONS Our data suggest that in the prostate Ptn functions as a regulator of both mesenchymal and epithelial proliferation, and that androgens regulate Ptn levels. © 2010 Wiley-Liss, Inc.
|
||||||||||
2011 |
Smith L, 'Good planning and serendipity: Exploiting the Cre/Lox system in the testis', Reproduction, 141 151-161 (2011) [C1] Over the past 20 years, genetic manipulation has revolutionised our understanding of male reproductive development and function. The advent of transgenic mouse lines has permitted... [more] Over the past 20 years, genetic manipulation has revolutionised our understanding of male reproductive development and function. The advent of transgenic mouse lines has permitted elegant dissection of previously intractable issues. The development of the Cre/Lox system, which has permitted spatial and temporal localisation of genetic manipulation, has expanded upon this, and now makes up one of the primary approaches underpinning our increasing understanding of testis development and function. The success of conditional gene targeting is largely reliant upon the choice of Cre recombinase expressing mouse line, which is required to specifically target the correct cell type at the correct time. Presupposition that Cre lines will behave as expected has been one of the main oversights in the design of Cre/Lox experiments, as in practice, many Cre lines are prone to ectopic expression (both temporal and spatial), transgene silencing or genetic background effects. Empirical validation of the spatiotemporal profile of Cre expression prior to undertaking conditional gene targeting studies is essential and can be achieved through a combination of molecular and immunohistochemical approaches, along with in vivo examination of reporter gene expression in targeted tissues. This paper details the key considerations associated with exploitation of the Cre/Lox system and highlights a variety of validated Cre lines that have utility for conditional gene targeting within the testis. © 2011 Society for Reproduction and Fertility.
|
||||||||||
2011 |
Denison FC, Smith LB, Muckett PJ, O'Hara L, Carling D, Woods A, 'LKB1 Is an Essential Regulator of Spermatozoa Release during Spermiation in the Mammalian Testis', PLOS ONE, 6 (2011) [C1]
|
||||||||||
2010 |
Welsh M, Moffat L, Jack L, McNeilly A, Brownstein D, Saunders PTK, et al., 'Deletion of Androgen Receptor in the Smooth Muscle of the Seminal Vesicles Impairs Secretory Function and Alters Its Responsiveness to Exogenous Testosterone and Estradiol', ENDOCRINOLOGY, 151 3374-3385 (2010)
|
||||||||||
2010 |
Welsh M, MacLeod DJ, Walker M, Smith LB, Sharpe RM, 'Critical androgen-sensitive periods of rat penis and clitoris development', INTERNATIONAL JOURNAL OF ANDROLOGY, 33 E144-E152 (2010)
|
||||||||||
2010 |
Willems A, De Gendt K, Allemeersch J, Smith LB, Welsh M, Swinnen JV, Verhoeven G, 'Early effects of Sertoli cell-selective androgen receptor ablation on testicular gene expression', INTERNATIONAL JOURNAL OF ANDROLOGY, 33 507-517 (2010)
|
||||||||||
2010 |
Welsh M, Sharpe RM, Moffat L, Atanassova N, Saunders PTK, Kilter S, et al., 'Androgen Action via Testicular Arteriole Smooth Muscle Cells Is Important for Leydig Cell Function, Vasomotion and Testicular Fluid Dynamics', PLOS ONE, 5 (2010)
|
||||||||||
2009 |
Welsh M, Sharpe RM, Walker M, Smith LB, Saunders PTK, 'New Insights into the Role of Androgens in Wolffian Duct Stabilization in Male and Female Rodents', ENDOCRINOLOGY, 150 2472-2480 (2009)
|
||||||||||
2009 |
Welsh M, Saunders PTK, Atanassova N, Sharpe RM, Smith LB, 'Androgen action via testicular peritubular myoid cells is essential for male fertility', FASEB JOURNAL, 23 4218-4230 (2009)
|
||||||||||
2009 |
Pastorelli LM, Wells S, Fray M, Smith A, Hough T, Harfe BD, et al., 'Genetic analyses reveal a requirement for Dicer1 in the mouse urogenital tract', Mammalian Genome, 20 140-151 (2009) Despite the increasing interest in other classes of small RNAs, microRNAs (miRNAs) remain the most widely investigated and have been shown to play a role in a number of different ... [more] Despite the increasing interest in other classes of small RNAs, microRNAs (miRNAs) remain the most widely investigated and have been shown to play a role in a number of different processes in mammals. Many studies investigating miRNA function focus on the processing enzyme Dicer1, which is an RNAseIII protein essential for the biogenesis of active miRNAs through its cleavage of precursor RNA molecules. General deletion of Dicer1 in the mouse confirms that miRNAs are essential for development because embryos lacking Dicer1 fail to reach the end of gastrulation. Here we investigate the role of Dicer1 in urogenital tract development. We utilised a conditional allele of the Dicer1 gene and two Cre-expressing lines, driven by HoxB7 and Amhr2, to investigate the effect of Dicer1 deletion on both male and female reproductive tract development. Data presented here highlight an essential role for Dicer1 in the correct morphogenesis and function of the female reproductive tract and confirm recent findings that suggest Dicer1 is required for female fertility. In addition, HoxB7:Cre-mediated deletion in ureteric bud derivatives leads to a spectrum of anomalies in both males and females, including hydronephrotic kidneys and kidney parenchymal cysts. Male reproductive tract development, however, remains largely unaffected in the absence of Dicer1. Thus, Dicer1 is required for development of the female reproductive tract and also normal kidney morphogenesis. © 2009 Springer Science+Business Media, LLC.
|
||||||||||
2008 |
Welsh M, Saunders PTK, Fisken M, Scott HM, Hutchison GR, Smith LB, Sharpe RM, 'Identification in rats of a programming window for reproductive tract masculinization, disruption of which leads to hypospadias and cryptorchidism', JOURNAL OF CLINICAL INVESTIGATION, 118 1479-1490 (2008)
|
||||||||||
2008 |
Smith L, Willan J, Warr N, Brook FA, Cheeseman M, Sharpe R, et al., 'The maestro (Mro) gene is dispensable for normal sexual development and fertility in mice', PLoS ONE, 3 (2008) The mammalian gonad arises as a bipotential primordium from which a testis or ovary develops depending on the chromosomal sex of the individual. We have previously used DNA microa... [more] The mammalian gonad arises as a bipotential primordium from which a testis or ovary develops depending on the chromosomal sex of the individual. We have previously used DNA microarrays to screen for novel genes controlling the developmental fate of the indifferent embryonic mouse gonad. Maestro (Mro), which encodes a HEAT-repeat protein, was originally identified as a gene exhibiting sexually dimorphic expression during mouse gonad development. Wholemount in situ hybridisation analysis revealed Mro to be expressed in the embryonic male gonad from approximately 11.5 days post coitum, prior to overt sexual differentiation. No significant expression was detected in female gonads at the same developmental stage. In order to address its physiological function, we have generated mice lacking Maestro using gene targeting. Male and female mice homozygous for a Mro null allele are viable and fertile. We examined gonad development in homozygous male embryos in detail and observed no differences when compared to wild-type controls. Immunohistochemical analysis of homozygous mutant testes of adult mice revealed no overt abnormalities. Expression profiling using DNA microarrays also indicated no significant differences between homozygote embryonic male gonads and controls. We conclude that Maestro is dispensable for normal male sexual development and fertility in laboratory mice; however, the Mro locus itself does have utility as a site for insertion of transgenes for future studies in the fields of sexual development and Sertoli cell function. © 2008 Smith et al.
|
||||||||||
2007 |
Frankenberg S, Smith L, Greenfield A, Zernicka-Goetz M, 'Novel gene expression patterns along the proximo-distal axis of the mouse embryo before gastrulation', BMC Developmental Biology, 7 (2007) Background. To date, the earliest stage at which the orientation of the anterior-posterior axis in the mouse embryo is distinguishable by asymmetric gene expression is shortly aft... [more] Background. To date, the earliest stage at which the orientation of the anterior-posterior axis in the mouse embryo is distinguishable by asymmetric gene expression is shortly after E5.5. At E5.5, prospective anterior markers are expressed at the distal tip of the embryo, whereas prospective posterior markers are expressed more proximally, close to the boundary with the extraembryonic region. Results. To contribute to elucidating the mechanisms underlying the events involved in early patterning of the mouse embryo, we have carried out a microarray screen to identify novel genes that are differentially expressed between the distal and proximal parts of the E5.5 embryo. Secondary screening of resulting candidates by in situ hybridisation at E5.5 and E6.5 revealed novel expression patterns for known and previously uncharacterised genes, including Peg10, Ctsz1, Cubilin, Jarid1b, Ndrg1, Sfmbt2, Gjb5, Talia and Plet1. The previously undescribed gene Talia and recently identified Plet1 are expressed specifically in the distal-most part of the extraembryonic ectoderm, adjacent to the epiblast, and are therefore potential candidates for regulating early patterning events. Talia and the previously described gene XE7 define a gene family highly conserved among metazoans and with a predicted protein structure suggestive of a post-transcriptional regulative function, whilst Plet1 appears to be mammal-specific and of unknown function. Conclusion. Our approach has allowed us to compare expression between dissected parts of the egg cylinder and has identified multiple genes with novel expression patterns at this developmental stage. These genes are potential candidates for regulating tissue interactions following implantation. © 2007 Frankenberg et al; licensee BioMed Central Ltd.
|
||||||||||
2006 |
Cox S, Smith L, Bogani D, Cheeseman M, Siggers P, Greenfield A, 'Sexually dimorphic expression of secreted frizzled-related (SFRP) genes in the developing mouse Müllerian duct.', Mol Reprod Dev, 73 1008-1016 (2006)
|
||||||||||
2005 |
Price TS, Regan R, Mott R, Hedman A, Honey B, Daniels RJ, et al., 'SW-ARRAY: A dynamic programming solution for the identification of copy-number changes in genomic DNA using array comparative genome hybridization data', Nucleic Acids Research, 33 3455-3464 (2005) Comparative genome hybridization (CGH) to DNA microarrays (array CGH) is a technique capable of detecting deletions and duplications in genomes at high resolution. However, array ... [more] Comparative genome hybridization (CGH) to DNA microarrays (array CGH) is a technique capable of detecting deletions and duplications in genomes at high resolution. However, array CGH studies of the human genome noting false negative and false positive results using large insert clones as probes have raised important concerns regarding the suitability of this approach for clinical diagnostic applications. Here, we adapt the Smith-Waterman dynamic-programming algorithm to provide a sensitive and robust analytic approach (SW-ARRAY) for detecting copy-number changes in array CGH data. In a blind series of hybridizations to arrays consisting of the entire tiling path for the terminal 2 Mb of human chromosome 16p, the method identified all monosomies between 267 and 1567 kb with a high degree of statistical significance and accurately located the boundaries of deletions in the range 267-1052 kb. The approach is unique in offering both a nonparametric segmentation procedure and a nonparametric test of significance. It is scalable and well-suited to high resolution whole genome array CGH studies that use array probes derived from large insert clones as well as PCR products and oligonucleotides. © The Author 2005. Published by Oxford University Press. All rights reserved.
|
||||||||||
2003 |
Smith L, Greenfield A, 'DNA microarrays and development', Human Molecular Genetics, 12 (2003) Gene expression is a central concept in molecular biology: its control, frequently exquisite in terms of cell specificity and timing, forms part of our explanation of most biologi... [more] Gene expression is a central concept in molecular biology: its control, frequently exquisite in terms of cell specificity and timing, forms part of our explanation of most biological processes. The importance of the control of gene expression for developmental biologists is made obvious by just considering the nature of their discipline. Development is the term we use to describe the coordination in time and space of numerous cellular activities such as mitosis, migration, differentiation and apoptosis. Understanding the role of genes in these processes thus necessitates the use of methods to determine patterns of transcription during development with a high degree of sensitivity and specificity, conventionally by in situ hybridization. However, there is a widespread conviction amongst biologists that the description of gene expression patterns is of no immediate functional relevance: definitive functional data are the exclusive prerogative of biochemistry and genetics. In this review of recent applications of DNA microarray technology by developmental biologists, we suggest that genome-wide expression profiling has met with some resistance owing to such preconceived ideas about the status of gene expression pattern descriptions and, in particular, the format in which these are delivered by microarrays.
|
||||||||||
2003 |
Smith L, Van Hateren N, Willan J, Romero R, Blanco G, Siggers P, et al., 'Candidate testis-determining gene, maestro (Mro), encodes a novel HEAT repeat protein', Developmental Dynamics, 227 600-607 (2003) Mammalian sex determination depends on the presence or absence of SRY transcripts in the embryonic gonad. Expression of SRY initiates a pathway of gene expression resulting in tes... [more] Mammalian sex determination depends on the presence or absence of SRY transcripts in the embryonic gonad. Expression of SRY initiates a pathway of gene expression resulting in testis development. Here, we describe a novel gene potentially functioning in this pathway using a cDNA microarray screen for genes exhibiting sexually dimorphic expression during murine gonad development. Maestro (Mro) transcripts are first detected in the developing male gonad before overt testis differentiation. By 12.5 days postcoitus (dpc), Mro transcription is restricted to the developing testis cords and its expression is not germ cell-dependent. No expression is observed in female gonads between 10.5 and 14.5 dpc. Maestro encodes a protein containing HEAT-like repeats that localizes to the nucleolus in cell transfection assays. Maestro maps to a region of mouse chromosome 18 containing a genetic modifier of XX sex reversal. We discuss the possible function of Maestro in light of these data. © 2003 Wiley-Liss, Inc.
|
||||||||||
2003 |
Smith L, Underhill P, Pritchard C, Tymowska-Lalanne Z, Abdul-Hussein S, Hilton H, et al., 'Single primer amplification (SPA) of cDNA for microarray expression analysis', Nucleic acids research, 31 e9 (2003) The potential of expression analysis using cDNA microarrays to address complex problems in a wide variety of biological contexts is now being realised. A limiting factor in such a... [more] The potential of expression analysis using cDNA microarrays to address complex problems in a wide variety of biological contexts is now being realised. A limiting factor in such analyses is often the amount of RNA required, usually tens of micrograms. To address this problem researchers have turned to methods of improving detection sensitivity, either through increasing fluorescent signal output per mRNA molecule or increasing the amount of target available for labelling by use of an amplification procedure. We present a novel DNA-based method in which an oligonucleotide is incorporated into the 3' end of cDNA during second-strand cDNA synthesis. This sequence provides an annealing site for a single complementary heel primer that directs Taq DNA polymerase amplification of cDNA following multiple cycles of denaturation, annealing and extension. The utility of this technique for transcriptome-wide screening of relative expression levels was compared to two alternative methodologies for production of labelled cDNA target, namely incorporation of fluorescent nucleotides by reverse transcriptase or the Klenow fragment. Labelled targets from two distinct mouse tissues, adult liver and kidney, were compared by hybridisation to a set of cDNA microarrays containing 6500 mouse cDNA probes. Here we demonstrate, through a dilution series of cDNA derived from 10 micro g of total RNA, that it is possible to produce datasets comparable to those produced with unamplified targets with the equivalent of 30 ng of total RNA. The utility of this technique for microarray analysis in cases where sample is limited is discussed.
|
||||||||||
2002 |
Siggers P, Smith L, Greenfield A, 'Sexually dimorphic expression of Gata-2 during mouse gonad development', Mechanisms of Development, 111 159-162 (2002) We report that Gata-2 is expressed in a sexually dimorphic fashion during mouse gonadogenesis. Gata-2 transcripts accumulate rapidly in the fetal ovary from 11.5 days post coitum ... [more] We report that Gata-2 is expressed in a sexually dimorphic fashion during mouse gonadogenesis. Gata-2 transcripts accumulate rapidly in the fetal ovary from 11.5 days post coitum (dpc) onwards, but are not detected in the fetal testis throughout the period studied (10.5-15.5 dpc). Ovarian expression of Gata-2 ceases by 15.5 dpc. Examination of ovaries from embryos homozygous for the extreme allele of c-kit(We) (Nature, 335, 88; Cell, 55, 185) demonstrates that ovarian Gata-2 expression is dependent upon the presence of germ cells. Comparative in situ hybridisation using the germ cell marker Oct4 (EMBO J., 8, 2543) indicates that Gata-2 transcripts are restricted to the germ cell lineage at 13.5 dpc. © 2002 Elsevier Science Ireland Ltd. All rights reserved.
|
||||||||||
2001 |
Ryder CD, Smith LB, Teakle GR, King GJ, 'Contrasting genome organisation: two regions of the Brassica oleracea genome compared with collinear regions of the Arabidopsis thaliana genome.', Genome, 44 808-817 (2001)
|
||||||||||
2000 |
Smith LB, King GJ, 'The distribution of BoCAL-a alleles in Brassica oleracea is consistent with a genetic model for curd development and domestication of the cauliflower', Molecular Breeding, 6 603-613 (2000) The characteristic curd of cauliflower (Brassica oleracea var. botrytis L.) consists of proliferating, arrested inflorescence and floral meristems. However, the origins and events... [more] The characteristic curd of cauliflower (Brassica oleracea var. botrytis L.) consists of proliferating, arrested inflorescence and floral meristems. However, the origins and events leading to the domestication of this important crop trait remain unclear. A similar phenotype observed in the ap1-1/cal-1 mutant of Arabidopsis thaliana led to speculation that the orthologous genes from B. oleracea may be responsible for this characteristic trait. We have carried out a detailed molecular and genetic study, which allows us to present a genetic model based on segregation of recessive alleles at specific, mapped loci of the candidate genes BoCAL and BoAP1. This accounts for differences in stage of arrest between cauliflower and Calabrese broccoli (B. oleracea var. italica Plenck), and predicts the intermediate stages of arrest similar to those observed in Sicilian Purple types. Association of alleles of BoCAL-a with curding phenotypes of B. oleracea is also demonstrated through a survey of crop accessions. Strong correlations exist between specific alleles of BoCAL-a and discrete inflorescence morphologies. These complementary lines of evidence suggest that the cauliflower curd arose in southern Italy from a heading Calabrese broccoli via an intermediate Sicilian crop type. PCR-based assays for the two key loci contributing to curd development are suitable for adoption in marker-assisted selection.
|
||||||||||
2000 |
Grimmond S, Van Hateren N, Siggers P, Arkell R, Larder R, Soares MB, et al., 'Sexually dimorphic expression of protease nexin-1 and vanin-1 in the developing mouse gonad prior to overt differentiation suggests a role in mammalian sexual development', Human Molecular Genetics, 9 1553-1560 (2000) The mammalian sex-determining pathway is controlled by the presence or absence of SRY expression in the embryonic gonad. Expression of SRY in males is believed to initiate a pathw... [more] The mammalian sex-determining pathway is controlled by the presence or absence of SRY expression in the embryonic gonad. Expression of SRY in males is believed to initiate a pathway of gene expression resulting in testis development. In the absence of SRY, ovary development ensues. Several genes have now been placed in this pathway but our understanding of it is far from complete and several functional classes of protein appear to be absent. Sex-determining genes frequently exhibit sexually dimorphic patterns of expression in the developing gonad both before and after overt differentiation of the testis or ovary. In order to identify additional sex-determining or gonadal differentiation genes we have examined gene expression in the developing gonads of the mouse using cDNA microarrays constructed from a normalized urogenital ridge library. We screened for genes exhibiting sexually dimorphic patterns of expression in the gonad at 12.5 and 13.5 days post-coitum, after overt gonad differentiation, by comparing complex cDNA probes derived from male and female gonadal tissue at these stages on microarrays. Using in situ hybridization analysis we show here that two genes identified by this screen, protease nexin-1 (Pn-1) and vanin-1 (Vnn1), exhibit male-specific expression prior to overt gonadal differentiation and are detected in the somatic portion of the developing gonad, suggesting a possible direct link to the testis-determining pathway for both genes.
|
||||||||||
Show 100 more journal articles |
Conference (3 outputs)
Year | Citation | Altmetrics | Link | ||
---|---|---|---|---|---|
2016 |
Macdonald J, Smith LB, Anderson RA, Mitchell RT, 'Spatiotemporal profiling of luteinising hormone/human choriogonadotropin receptor in the human fetal testis', LANCET, Royal Coll Phys, London, ENGLAND (2016)
|
||||
2010 | McInnes KJ, Smith LB, Saunders PTK, Andrew R, Walker BR, 'Adipose-Specific Knockout of Androgen Receptors in Male Mice Results in Altered Adipose Gene Expression, Hyperinsulinemia and Hypertriglyceridemia without Obesity', ENDOCRINE REVIEWS, San Diego, CA (2010) | ||||
2010 | Welsh M, Moffat L, McNeilly A, Saunders PTK, Sharpe RM, Smith LB, 'New Model for Age-Related Prostatic Disease: Smooth Muscle Cell-Specific Knockout of Androgen Receptor.', ENDOCRINE REVIEWS, San Diego, CA (2010) |
Other (1 outputs)
Year | Citation | Altmetrics | Link | |||||
---|---|---|---|---|---|---|---|---|
Sararols P, Stévant I, Neirijnck Y, Rebourcet D, Darbey A, Curley MK, et al., 'Specific transcriptomic signatures and dual regulation of steroidogenesis between fetal and adult mouse Leydig cells', Cold Spring Harbor Laboratory [O1]
|
Thesis / Dissertation (1 outputs)
Year | Citation | Altmetrics | Link | ||
---|---|---|---|---|---|
2018 |
Gannon A-L, Gannon A-L, Determining the role of androgen receptor and glucocorticoid receptor in the rodent adrenal cortex through conditional gene targeting, University of Edinburgh (2018)
|
Grants and Funding
Summary
Number of grants | 29 |
---|---|
Total funding | $22,228,293 |
Click on a grant title below to expand the full details for that specific grant.
20221 grants / $733,195
Adrenal-Targeted Nanobiotechnology: A Novel Therapy for Adrenal Disease$733,195
Funding body: NHMRC (National Health & Medical Research Council)
Funding body | NHMRC (National Health & Medical Research Council) |
---|---|
Project Team | Professor Lee Smith, Doctor Anne-Louise Gannon, Doctor Roger Liang |
Scheme | Ideas Grants |
Role | Lead |
Funding Start | 2022 |
Funding Finish | 2024 |
GNo | G2100526 |
Type Of Funding | C1100 - Aust Competitive - NHMRC |
Category | 1100 |
UON | Y |
20211 grants / $325,846
2021 HMRI MRSP - Pregnancy and Reproduction Program$325,846
Funding body: NSW Ministry of Health
Funding body | NSW Ministry of Health |
---|---|
Project Team | Laureate Professor Roger Smith, Laureate Professor John Aitken, Professor Craig Pennell, Professor Brett Nixon, Associate Professor Kirsty Pringle, Associate Professor Mark Baker, Professor Jon Hirst, Doctor Elizabeth Bromfield, Doctor Jonathan Paul, Doctor Geoffry De Iuliis, Doctor Yogavijayan Kandasamy, Doctor Jessie Sutherland, Professor Lee Smith |
Scheme | Medical Research Support Program (MRSP) |
Role | Investigator |
Funding Start | 2021 |
Funding Finish | 2021 |
GNo | G2001363 |
Type Of Funding | C2400 – Aust StateTerritoryLocal – Other |
Category | 2400 |
UON | Y |
20203 grants / $2,383,433
Development of nanopharmaceutical strategies for the sterilization of domestic cats and dogs$1,648,882
Funding body: Found Animals Foundation Inc
Funding body | Found Animals Foundation Inc |
---|---|
Project Team | Professor Lee Smith, Professor Lee Smith, Laureate Professor John Aitken, Doctor Roger Liang, Kari (CHJ) Albers-Wolthers, Dr Pamela Brown |
Scheme | Michelson Grants in Reproductive Biology |
Role | Lead |
Funding Start | 2020 |
Funding Finish | 2022 |
GNo | G1800032 |
Type Of Funding | C3500 – International Not-for profit |
Category | 3500 |
UON | Y |
MRSP 2020 Pregnancy and Reproduction Program$425,758
Funding body: NSW Ministry of Health
Funding body | NSW Ministry of Health |
---|---|
Project Team | Laureate Professor Roger Smith, Laureate Professor John Aitken, Professor Craig Pennell, Professor Lee Smith, Professor Jon Hirst, Professor Brett Nixon, Associate Professor Kirsty Pringle, Doctor Jonathan Paul, Doctor Jessie Sutherland |
Scheme | Medical Research Support Program (MRSP) |
Role | Investigator |
Funding Start | 2020 |
Funding Finish | 2021 |
GNo | G1901541 |
Type Of Funding | C2400 – Aust StateTerritoryLocal – Other |
Category | 2400 |
UON | Y |
Translation of an androgen-miRNA sterilant: pre-clinical validation & a clinical trial in cats & dogs. Year 4 funding continuation. $308,793
Funding body: Found Animals Foundation Inc
Funding body | Found Animals Foundation Inc |
---|---|
Project Team | Professor Lee Smith, Dr Pamela Brown |
Scheme | Michelson Grants in Reproductive Biology |
Role | Lead |
Funding Start | 2020 |
Funding Finish | 2021 |
GNo | |
Type Of Funding | International - Competitive |
Category | 3IFA |
UON | N |
20191 grants / $521,327
The Importance of Classical Versus Backdoor Androgen Production Pathways in Masculinisation, Fertility and Lifelong Male Health$521,327
Funding body: NHMRC (National Health & Medical Research Council)
Funding body | NHMRC (National Health & Medical Research Council) |
---|---|
Project Team | Professor Lee Smith, Doctor Diane Rebourcet |
Scheme | Project Grant |
Role | Lead |
Funding Start | 2019 |
Funding Finish | 2021 |
GNo | G1800098 |
Type Of Funding | C1100 - Aust Competitive - NHMRC |
Category | 1100 |
UON | Y |
20171 grants / $1,016,775
Translation of an androgen-miRNA sterilant$1,016,775
Funding body: Found Animals Foundation Inc
Funding body | Found Animals Foundation Inc |
---|---|
Project Team | Prof LB Smith (PI) |
Scheme | Michelson Grants in Reproductive Biology |
Role | Lead |
Funding Start | 2017 |
Funding Finish | 2020 |
GNo | |
Type Of Funding | External |
Category | EXTE |
UON | N |
20164 grants / $4,757,964
Androgens: Unlocking the key drivers of men's health$3,749,564
Funding body: Medical Research Council (UK)
Funding body | Medical Research Council (UK) |
---|---|
Project Team | Prof LB Smith (PI) |
Scheme | Programme Grant |
Role | Lead |
Funding Start | 2016 |
Funding Finish | 2021 |
GNo | |
Type Of Funding | External |
Category | EXTE |
UON | N |
How does pituitary androgen signalling support lifelong health and wellbeing? An integrated transgenic and systems biology approach$920,072
Funding body: Biotechnology and Biological Sciences Research Council (BBSRC)
Funding body | Biotechnology and Biological Sciences Research Council (BBSRC) |
---|---|
Project Team | Prof LB Smith (PI) |
Scheme | Research Grant |
Role | Lead |
Funding Start | 2016 |
Funding Finish | 2019 |
GNo | |
Type Of Funding | External |
Category | EXTE |
UON | N |
Role of vascular androgen receptor in advanced atherosclerosis$87,199
Funding body: Wellcome Trust
Funding body | Wellcome Trust |
---|---|
Scheme | ISSF Project Grant |
Role | Investigator |
Funding Start | 2016 |
Funding Finish | 2017 |
GNo | |
Type Of Funding | External |
Category | EXTE |
UON | N |
Society for Reproduction and Fertility – International Collaboration$1,129
Funding body: Society for Reproduction and Fertility
Funding body | Society for Reproduction and Fertility |
---|---|
Scheme | Travel Award |
Role | Lead |
Funding Start | 2016 |
Funding Finish | 2016 |
GNo | |
Type Of Funding | External |
Category | EXTE |
UON | N |
20152 grants / $145,317
PhD tissue repair studentship award (open competition)$141,415
Funding body: University of Edinburgh
Funding body | University of Edinburgh |
---|---|
Project Team | Prof LB Smith (PI) |
Scheme | Award |
Role | Lead |
Funding Start | 2015 |
Funding Finish | 2018 |
GNo | |
Type Of Funding | Internal |
Category | INTE |
UON | N |
A new UK-wide Virtual Centre for men's health research$3,902
Funding body: University of Edinburgh
Funding body | University of Edinburgh |
---|---|
Project Team | Prof LB Smith (PI) |
Scheme | Innovation Initiative Grant |
Role | Lead |
Funding Start | 2015 |
Funding Finish | 2016 |
GNo | |
Type Of Funding | Internal |
Category | INTE |
UON | N |
20141 grants / $111,678
PhD studentship award (open competition)$111,678
Funding body: University of Edinburgh
Funding body | University of Edinburgh |
---|---|
Project Team | Prof LB Smith (PI) |
Scheme | Award |
Role | Lead |
Funding Start | 2014 |
Funding Finish | 2017 |
GNo | |
Type Of Funding | External |
Category | EXTE |
UON | N |
20135 grants / $866,176
Sterilization via disruption of androgen signaling in Sertoli and Granulosa cells: Proof of concept study in mice$633,049
Funding body: Found Animals Foundation Inc
Funding body | Found Animals Foundation Inc |
---|---|
Project Team | Dr LB Smith (PI), Dr P Brown |
Scheme | Michelson Grants in Reproductive Biology |
Role | Lead |
Funding Start | 2013 |
Funding Finish | 2016 |
GNo | |
Type Of Funding | Internal |
Category | INTE |
UON | N |
PhD Studentship Award: Establishing the cause-consequence relationship between age-related reduction in androgens and normal ageing processes $113,400
Funding body: EASTBio
Funding body | EASTBio |
---|---|
Project Team | Prof LB Smith (PI) |
Scheme | BBSRC |
Role | Lead |
Funding Start | 2013 |
Funding Finish | 2017 |
GNo | |
Type Of Funding | External |
Category | EXTE |
UON | N |
Charles Darwin PhD Scholarship with Gordon Lennie Bursary Award$70,115
Funding body: University of Edinburgh
Funding body | University of Edinburgh |
---|---|
Project Team | Tina Tsai (Student), Dr LB Smith (PI) |
Scheme | Award |
Role | Lead |
Funding Start | 2013 |
Funding Finish | 2016 |
GNo | |
Type Of Funding | Internal |
Category | INTE |
UON | N |
Global PhD Scholarship Award$46,744
Funding body: University of Edinburgh
Funding body | University of Edinburgh |
---|---|
Project Team | Tina Tsai (Student), Dr LB Smith (PI) |
Scheme | Award |
Role | Lead |
Funding Start | 2013 |
Funding Finish | 2016 |
GNo | |
Type Of Funding | Internal |
Category | INTE |
UON | N |
Characterization of a novel mouse model of induced androgen receptor expression $2,868
Funding body: Medical Research Scotland
Funding body | Medical Research Scotland |
---|---|
Project Team | Prof LB Smith (PI) |
Scheme | Research Grant |
Role | Investigator |
Funding Start | 2013 |
Funding Finish | 2013 |
GNo | |
Type Of Funding | External |
Category | EXTE |
UON | N |
20123 grants / $1,750,708
Integrating systems biology and transgenic technologies to unlock the secrets of Sertoli cell development and function$1,177,061
Funding body: Biotechnology and Biological Sciences Research Council (BBSRC)
Funding body | Biotechnology and Biological Sciences Research Council (BBSRC) |
---|---|
Project Team | Dr LB Smith (PI), Prof P O’Shaughnessy, Prof T Freeman |
Scheme | Research Grant |
Role | Lead |
Funding Start | 2012 |
Funding Finish | 2015 |
GNo | |
Type Of Funding | External |
Category | EXTE |
UON | N |
Cell-Specific Action of Androgen Receptor in Cardiovascular Function, Response and Repair$440,590
Funding body: British Heart Foundation
Funding body | British Heart Foundation |
---|---|
Project Team | Dr LB Smith (PI), Dr PWF Hadoke, Dr M Denvir |
Scheme | Research Grant |
Role | Lead |
Funding Start | 2012 |
Funding Finish | 2015 |
GNo | |
Type Of Funding | External |
Category | EXTE |
UON | N |
Control of Leydig cell function and regeneration$133,057
Funding body: MRC Medical Research Council UK
Funding body | MRC Medical Research Council UK |
---|---|
Project Team | Dr LB Smith (PI), Prof Richard Sharpe |
Scheme | Research Grant |
Role | Lead |
Funding Start | 2012 |
Funding Finish | 2015 |
GNo | |
Type Of Funding | Internal |
Category | INTE |
UON | N |
20112 grants / $8,998,615
Testis Development and Function in Relation to Disorders of Reproductive and General Health in Males$5,059,479
Funding body: MRC Medical Research Council UK
Funding body | MRC Medical Research Council UK |
---|---|
Project Team | Prof RM Sharpe (PI), Dr LB Smith |
Scheme | Research Grant |
Role | Investigator |
Funding Start | 2011 |
Funding Finish | 2016 |
GNo | |
Type Of Funding | External |
Category | EXTE |
UON | N |
Genetic and Hormonal Determinants of Male Reproductive Health and Fertility$3,939,136
Funding body: MRC Medical Research Council UK
Funding body | MRC Medical Research Council UK |
---|---|
Project Team | Dr LB Smith (PI) |
Scheme | Research Grant |
Role | Lead |
Funding Start | 2011 |
Funding Finish | 2016 |
GNo | |
Type Of Funding | External |
Category | EXTE |
UON | N |
20092 grants / $178,648
Cell-cell synergism in androgen control of testis function$172,447
Funding body: MRC Medical Research Council UK
Funding body | MRC Medical Research Council UK |
---|---|
Project Team | Dr LB Smith (PI) Prof Philippa Saunders |
Scheme | PhD Studentship |
Role | Lead |
Funding Start | 2009 |
Funding Finish | 2012 |
GNo | |
Type Of Funding | External |
Category | EXTE |
UON | N |
Identifying a novel gene that causes obesity. Investigators$6,200
Funding body: University of Edinburgh
Funding body | University of Edinburgh |
---|---|
Project Team | Dr K McInnes (PI), Dr LB Smith |
Scheme | Research Grant |
Role | Investigator |
Funding Start | 2009 |
Funding Finish | 2009 |
GNo | |
Type Of Funding | Internal |
Category | INTE |
UON | N |
20082 grants / $232,292
Genetic mapping of a novel, spontaneous, early-onset mouse model of Aortic Aneurysm with acute Dissection (AAD)$210,787
Funding body: British Heart Foundation
Funding body | British Heart Foundation |
---|---|
Project Team | Dr LB Smith (PI), Dr PWF Hadoke, Dr M Denvir, Dr D Brownstein |
Scheme | Research Grant |
Role | Lead |
Funding Start | 2008 |
Funding Finish | 2010 |
GNo | |
Type Of Funding | External |
Category | EXTE |
UON | N |
Androgens and sex-specific risk of cardiovascular disease$21,505
Funding body: Tenovus Scotland
Funding body | Tenovus Scotland |
---|---|
Project Team | Dr LB Smith (PI), Dr PWF Hadoke, Dr M Denvir |
Scheme | Research Grant |
Role | Lead |
Funding Start | 2008 |
Funding Finish | 2009 |
GNo | |
Type Of Funding | External |
Category | EXTE |
UON | N |
20071 grants / $206,319
Androgen signalling in a novel model of male infertility$206,319
Funding body: MRC Medical Research Council UK
Funding body | MRC Medical Research Council UK |
---|---|
Project Team | Dr LB Smith (PI), Prof Philippa Saunders |
Scheme | PhD Studentship |
Role | Lead |
Funding Start | 2007 |
Funding Finish | 2010 |
GNo | |
Type Of Funding | Internal |
Category | INTE |
UON | N |
Research Supervision
Number of supervisions
Current Supervision
Commenced | Level of Study | Research Title | Program | Supervisor Type |
---|---|---|---|---|
2020 | PhD | Comparative roles of distinct testosterone production pathways in men | Genetics, Faculty of Science and Information Technology The University of Newcastle | Principal Supervisor |
2020 | PhD | The Importance of Classical Versus Backdoor Androgen Production Pathways in Masculinisation, Fertility and Lifelong Male Health | PhD (Biological Sciences), College of Engineering, Science and Environment, The University of Newcastle | Co-Supervisor |
Past Supervision
Year | Level of Study | Research Title | Program | Supervisor Type |
---|---|---|---|---|
2018 | PhD | Germ cell origins of testicular cancer | Medical Science, University of Edinburgh | Co-Supervisor |
2018 | PhD | The impact of ageing on testicular endocrinology and function | Medical Science, University of Edinburgh | Principal Supervisor |
2018 | PhD | Tissue repair in the testis through gene therapy | Medical Science, University of Edinburgh | Principal Supervisor |
2017 | PhD | The role of androgen signalling in the adrenal gland | Medical Science, University of Edinburgh | Principal Supervisor |
2017 | Masters | The role of Srd5a1 in testicular function | Medical Science, University of Edinburgh | Co-Supervisor |
2016 | Masters | Defining pituitary stem cell populations in the male mouse | Medical Science, University of Edinburgh | Co-Supervisor |
2015 | PhD | Androgen signalling in the endometrium | Medical Science, University of Edinburgh | Co-Supervisor |
2015 | PhD | Impact of estrogen receptor antagonists on male reproductive development and function | Medical Science, University of Edinburgh | Principal Supervisor |
2015 | PhD | Macrophages in testis development and function | Medical Science, University of Edinburgh | Principal Supervisor |
2014 | Masters | The role of Sertoli cell population size in testis function | Medical Science, University of Edinburgh | Co-Supervisor |
2014 | Masters | The role of androgen receptor in pituitary function | Medical Science, University of Edinburgh | Co-Supervisor |
2013 | PhD | Leydig stem cell development and function | Medical Science, University of Edinburgh | Co-Supervisor |
2012 | Honours | 3D imaging of Sertoli cells | Medical Science, University of Edinburgh | Principal Supervisor |
2011 | Masters | Androgens in cardiovascular disease | Medical Science, University of Edinburgh | Co-Supervisor |
2011 | PhD | Characterisation of the male programming window during development | Medical Science, University of Edinburgh | Co-Supervisor |
2010 | PhD | Androgen Receptor signalling in the pituitary | Medical Science, University of Edinburgh | Principal Supervisor |
2009 | Masters | Androgen signalling in prostate smooth muscle | Medical Science, University of Edinburgh | Principal Supervisor |
2008 | Masters | New genes in male reproductive development | Medical Science, University of Edinburgh | Principal Supervisor |
2006 | Masters | characterisation of a Pax2-GFP reproductive system | Medical Science, University of Edinburgh | Sole Supervisor |
Research Opportunities
PhD Scholarships
1x PhD Scholarships (stipend and fees) for domestic students are available for August 2020
PHD
School of Environmental and Life Sciences
1/8/2020 - 30/1/2024
Contact
Professor Lee Smith
University of Newcastle
Office PVC - Science
lee.smith@newcastle.edu.au
PhD Scholarships
2x PhD Scholarships (stipend and fees) for domestic students are available for December 2020
PHD
School of Environmental and Life Sciences
1/12/2020 - 31/5/2024
Contact
Professor Lee Smith
University of Newcastle
Office PVC - Science
lee.smith@newcastle.edu.au
News
$4.5m in NHMRC Ideas Grants supports quest to improve human health
November 8, 2021
‘Sneaky’ sperm particles hitchhike around the body
March 25, 2021
$1 million food facilities unveiled at Ourimbah
March 16, 2020
Opening new doors to improve male health
February 1, 2019
Professor Lee Smith
Position
Honorary Professor
Office of the PVC, Engineering, Science and Environment
School of Environmental and Life Sciences
College of Engineering, Science and Environment
Contact Details
lee.smith@newcastle.edu.au | |
Mobile | 0437075039 |
Fax | (02) 4921 7949 |
Link | Personal webpage |
Office
Room | NIER-C 131 |
---|---|
Building | NIER C-Block |
Location | Callaghan University Drive Callaghan, NSW 2308 Australia |